Dasatinib in Preventing Oxaliplatin-Induced Peripheral Neuropathy in Patients With Colorectal Cancer Receiving FOLFOX and Bevacizumab
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|ClinicalTrials.gov Identifier: NCT04164069|
Recruitment Status : Recruiting
First Posted : November 15, 2019
Last Update Posted : July 31, 2020
|Condition or disease||Intervention/treatment||Phase|
|Advanced Colorectal Carcinoma Metastatic Colorectal Carcinoma Stage IV Colorectal Cancer AJCC v8 Stage IVA Colorectal Cancer AJCC v8 Stage IVB Colorectal Cancer AJCC v8 Stage IVC Colorectal Cancer AJCC v8||Biological: Bevacizumab Drug: Dasatinib Drug: Fluorouracil Drug: Leucovorin Drug: Leucovorin Calcium Drug: Oxaliplatin Other: Quality-of-Life Assessment||Phase 1|
I. To determine the recommended phase 2 dose (RP2D) of dasatinib in combination with oxaliplatin and fluorouracil (5FU) (modified version 6 regimen of leucovorin, fluorouracil and oxaliplatin [mFOLFOX6]) with or without bevacizumab in patients with metastatic colorectal cancer, defined as the lowest intermittent dose of dasatinib that affects serum biomarkers of OCT2 without influencing the pharmacokinetic properties of oxaliplatin.
II. To determine the toxicity profile (based on Chemotherapy-Induced Peripheral Neuropathy [CIPN]20 and Common Terminology Criteria for Adverse Events [CTCAE] version [v.] 5.0) of dasatinib in combination with oxaliplatin/5-FU/bevacizumab in patients with colorectal cancer.
I. To evaluate the influence of dasatinib on the pharmacokinetics of oxaliplatin and vice versa in these patients.
OUTLINE: This is a dose-escalation study of dasatinib.
Patients receive oxaliplatin intravenously (IV) over 2 hours, leucovorin IV over 2 hours, fluorouracil slow IV push over 2-4 minutes followed by continuous infusion over 46 hours on days 1 and 15. Patients also receive dasatinib orally (PO) once daily (QD) on days 14, 15, and 28 of cycle 1 and day 1 of cycle 2. Patients may receive bevacizumab IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for up to cycle 3 day 1 in the absence of disease progression or unacceptable toxicity.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase Ib Adaptive Study Dasatinib for the Prevention of Oxaliplatin-Induced Neuropathy in Patients With Metastatic Colorectal Cancer Receiving FOLFOX Chemotherapy and Bevacizumab|
|Actual Study Start Date :||December 12, 2019|
|Estimated Primary Completion Date :||December 31, 2021|
|Estimated Study Completion Date :||December 31, 2021|
Experimental: Prevention (dasatinib, mFOLFOX, bevacizumab)
Patients receive oxaliplatin IV over 2 hours, leucovorin IV over 2 hours, fluorouracil slow IV push over 2-4 minutes followed by continuous infusion over 46 hours on days 1 and 15. Patients also receive dasatinib PO QD on days 14, 15, and 28 of cycle 1 and day 1 of cycle 2. Patients may receive bevacizumab IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for up to cycle 3 day 1 in the absence of disease progression or unacceptable toxicity.
Other Name: Folinic acid
Drug: Leucovorin Calcium
Other: Quality-of-Life Assessment
Other Name: Quality of Life Assessment
- Recommended phase II dose (RP2D) of dasatinib [ Time Frame: Up to 14 days ]The RP2D will be defined as the lowest intermittent dose of dasatinib that affects serum biomarkers of OCT2 without influencing the pharmacokinetic properties of oxaliplatin.
- Incidence of adverse events [ Time Frame: At the end of Cycle 1 (cycle length is 28 days) ]The dose-limiting toxicity and toxicity profile will be based using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 and Chemotherapy-Induced Peripheral Neuropathy (CIPN) 20. Toxicity will be defined as adverse events deemed to be at least possibly related to dasatinib treatment. Adverse events and toxicities will be summarized by dose level, and will tabulate these events by type and severity. Will summarize the numbers of patients who required dose reductions in dasatinib or oxaliplatin and the cumulative doses received. The CIPN20 will be measured in these subjects, and will be summarized within and across dose levels, and will be used to support and inform assumptions for a subsequent phase 2 trial.
- Dasatinib on pharmacokinetics (PK) of oxaliplatin [ Time Frame: Baseline, days 1, 2, and 14 ]Objective is to evaluate the influence of dasatinib on the pharmacokinetics of oxaliplatin and vice versa. Oxaliplatin PK will be measured at pre-dose, 1 hour, immediately prior to end of infusion of oxaliplatin, and 0.5, 1, 2, 4, and 24 hours after end of infusion on day 1; Dasatinib PK will be measured at pre-dose and 0.5, 1.5, 2.5, 3, 4.5, and 6.5 hours after taking dasatinib on day 14; PK of dasatinib and oxaliplatin will be measured on day 15 pre-dose of dasatinib, prior to starting oxaliplatin infusion, 1 hour after start of oxaliplatin infusion, immediately prior to end of infusion with oxaliplatin, and at 0.5, 1, 2, 4, and 24 hours after end of oxaliplatin infusion. PK parameters calculated using standard non-compartmental methods, and non-linear mixed effect models will be created to inform the use of limited-sampling strategies for subsequent confirmatory studies. Area Under the Curve [AUC] will be calculated for each drug Oxaliplatin - ug x h/ml and Dasatinib- ng x h/ml
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04164069
|Contact: The Ohio State University Comprehensive Cancer Center||1-800-293-5066||OSUCCCClinicaltrial@osumc.edu|
|United States, Ohio|
|Ohio State University Comprehensive Cancer Center||Recruiting|
|Columbus, Ohio, United States, 43210|
|Contact: Anne M. Noonan, MD 614-685-6912 email@example.com|
|Principal Investigator: Anne M. Noonan, MF|
|Principal Investigator:||Anne M Noonan, MBBChBAO, MSc||Ohio State University Comprehensive Cancer Center|